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NM_000018.4(ACADVL):c.505A>G (p.Met169Val) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 10, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001200825.3

Allele description [Variation Report for NM_000018.4(ACADVL):c.505A>G (p.Met169Val)]

NM_000018.4(ACADVL):c.505A>G (p.Met169Val)

Gene:
ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000018.4(ACADVL):c.505A>G (p.Met169Val)
HGVS:
  • NC_000017.11:g.7221565A>G
  • NG_007975.1:g.6732A>G
  • NG_008391.2:g.3486T>C
  • NM_000018.4:c.505A>GMANE SELECT
  • NM_001033859.3:c.439A>G
  • NM_001270447.2:c.574A>G
  • NM_001270448.2:c.277A>G
  • NP_000009.1:p.Met169Val
  • NP_001029031.1:p.Met147Val
  • NP_001257376.1:p.Met192Val
  • NP_001257377.1:p.Met93Val
  • NC_000017.10:g.7124884A>G
  • NC_000017.10:g.7124884A>G
  • NM_000018.3:c.505A>G
Protein change:
M147V
Links:
dbSNP: rs2071227343
NCBI 1000 Genomes Browser:
rs2071227343
Molecular consequence:
  • NM_000018.4:c.505A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001033859.3:c.439A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270447.2:c.574A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270448.2:c.277A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Very long chain acyl-CoA dehydrogenase deficiency (ACADVLD)
Synonyms:
VLCAD deficiency
Identifiers:
MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001365026Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Nov 1, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004261829Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Dec 10, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001365026.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The NM_000018.3:c.505A>G (NP_000009.1:p.Met169Val) [GRCH38: NC_000017.11:g.7221565A>G] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PM1

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004261829.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 169 of the ACADVL protein (p.Met169Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 932865). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACADVL protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024